Dupixent Shows Positive Results for Children Under 12 with Eosinophilic Esophagitis in Phase 3 Trial
Dupilumab (Dupixent) is the first medicine to improve signs of eosinophilic esophagitis and support weight gain in children ages 1 to 11, for whom there are no currently approved treatments.
Dupilumab (Dupixent; Regeneron, Sanofi) showed positive results in children 1 to 11 years with eosinophilic esophagitis (EoE) in a phase 3 trial, according to an announcement from Regeneron Pharmaceuticals, Inc and Sanofi.
The study is the first and only investigational phase 3 trial to show positive results in young children, according to the release. Currently, there are no approved treatments for children with EoE under 12 years of age.
"Dupixent is the first medicine to alleviate key signs of eosinophilic esophagitis in children as young as 1 year of age in a phase 3 trial. The efficacy of Dupixent demonstrates that in this age group, as in adults, IL-4 and IL-13 are key drivers of the type 2 inflammation underlying this debilitating disease," said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron, and a principal inventor of Dupixent, in a statement. "Eosinophilic esophagitis can turn the basic and life-sustaining act of eating into a painful experience at a point in children's lives when proper nutrition and achieving a healthy weight is critical to ensuring they grow and thrive. The positive results from this phase 3 pediatric trial show Dupixent has the potential to improve signs of eosinophilic esophagitis and support healthy weight gain in children from their first birthday."
The phase 3 trial assessed the investigational use of dupilumab in children aged 1 to 11 years with EoE. The trial included 102 children in this age group, 98% of whom had at least 1 co-existing type 1 inflammatory disease at baseline.
The study randomized 37 participants to receive a higher dose regimen of dupilumab, 31 to receive a low-dose regimen, and 34 to the placebo group, with dose regimens based on body weight. The trial met its primary endpoint of histological disease remission at 16 weeks with both the higher and lower dose weight-tiered regimens.
At 16 weeks, 68% of children on higher dose dupilumab and 58% of patients on lower dose dupilumab achieved the primary end point of significant histological disease remission (peak esophageal intraepithelial eosinophil count of ≤6 eosinophils [eos]/high power field [hpf], p < 0.0001). Only 3% of children on placebo achieved this primary end point at 16 weeks (p < 0.0001).
Children receiving the higher dose of dupilumab saw additional changes at week 16. They saw an 86% reduction in peak esophageal intraepithelial eosinophil count from baseline, compared to a 21% increase for placebo (p < 0.0001).
A 0.88 and 0.84 reduction from baseline in disease severity and extent, respectively, were observed, as measured at the microscopic level in biopsy specimens compared to a 0.02 and 0.05 increase for placebo (both p < 0.001).
Participants on the higher dose regimen experienced a 3.5-point reduction in abnormal endoscopic findings from baseline. Participants receiving a placebo experienced only a 0.3-point increase.
Caregivers reported a numerical improvement in the proportion of days children experienced symptoms of EoE from baseline, compared to placebo; however, this finding was not statistically significant.
A 3.09 percentile increase in body weight for age percentile from baseline was achieved for patients on the higher dose regimen, compared with 0.29 for placebo.
Researchers also analyzed histological, anatomic, and cellular secondary endpoints for the lower dose group. All were considered nominally significant and generally comparable with the higher dose.
Safety results observed in the study were consistent with the known safety profile of Dupixent in its approved EoE indication for children and adults aged 12 years and older who weigh at least 40 kg. Rates of adverse events (AEs) in the study showed that for the 16-week treatment period, overall rates of AEs were 79% for dupilumab and 91% for placebo. Rates of treatment discontinuation due to AEs prior to week 16 was 0% for dupilumab, compared with 6% for placebo.
Researchers plan to share more detailed results of the study at an upcoming medical meeting.
"We are incredibly excited to share results from this phase 3 pivotal trial evaluating Dupixent in young children suffering from eosinophilic esophagitis—the first ever to show positive results across a variety of primary and secondary endpoints. The lack of treatment options for children living with eosinophilic esophagitis leaves many caregivers with the stress and burden of adapting their child's meals and their entire family's daily schedules to ensure healthy growth and development. In some cases, they must resort to off-label use of poorly studied treatments like steroids that can pose serious health risks when used long term," Naimish Patel, MD, senior vice president, head of Global Development, Immunology and Inflammation at Sanofi said in a statement. "The faster and larger than anticipated enrollment in this trial further emphasizes the unmet treatment needs for children with EoE and underscores the significance of these first-ever positive results."
The FDA approved Dupixent 300 mg weekly to treat patients with EoE 12 years of age or older and weighing at least 40 kg in May 2022, after granting the medicine priority review.
However, the use of dupilumab in children with EoE aged 1 to 11 years is currently under clinical development. The safety and efficacy of the treatment for this population has not been fully evaluated by any regulatory authority.
Dupixent (dupilumab) phase 3 trial shows positive results in children 1 to 11 years of age with eosinophilic esophagitis [press release]. Tarrytown, NY: Regeneron Pharmaceuticals Inc; July 14, 2022. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-phase-3-trial-shows-positive-results. Accessed July 15, 2022.